Crystallization is a critical operation in the manufacture of pharmaceutical compounds. The crystallization process as part of the synthesis of an API affects the API crystal properties such as purity, polymorphic form, and particle size. Optimization of the crystallization process is important for API product quality as well as for process efficiency and high yield. Crystal properties also significantly impact the downstream processing. Another important aspect of crystallization development involves particle engineering to obtain desired particle size to meet the biopharmaceutical performance requirements.
For poorly soluble compounds, it is imperative to have small particle size in order to obtain maximum surface area and thus dissolution rate, which is usually a critical factor in improving bioavailability. It is not common or straightforward to achieve particle size uniformly below 10-20 μm by crystallization. Hence, many compounds are jet-milled to 10-20 μm, an expensive and highly energy intensive operation. Furthermore, oftentimes milled particles show non-uniform particle size distribution, poor powder flow, and low bulk density which cause difficult powder handling, formulation blending, and poor product content uniformity of drug product.